This renewal of a Fogarty International Research Collaboration Award builds on collaboration between the P.I., Dr. Fie Luo, in Beijing China and Drs. Jingyu Chang and D. Woodward at the Neuroscience Research Institute of North Carolina. The goal was to coordinate a common effort to understand the time course of effect and mechanisms of action of deep brain stimulation on different brain structures for Parkinson's disease, epilepsy control, and related brain functions. Initial studies focused on restoration of function in models of Parkinson's disease in rodent. A major effort included sharing and establishing advanced instrumentation for combined stimulation and recording at Dr. Luo's laboratory that was developed at the USA site specifically for these studies. Success of our joint effort led to the appointment of Dr. Lou to Professor along with new laboratory resources at the Institute of Psychology Chinese Academy of Science. Our group is now positioned to expand substantially the research theme of DBS mechanism to include regulation of central pain pathways under neuropathic conditions. Continual development of new recording capabilities at the North Carolina site will expand the capacities at Beijing in parallel with other supported groups. The goal of the current study is to elucidate mechanisms underlying effective deep brain stimulation (DBS) under chronic pain conditions. Aim 1 is to employ ensemble neuron recording in multiple regions to investigate the dynamic changes of ensemble neural activity in the thalamocortical pathways during the time course following the induction of pain by local inflammation or by ligation of spinal nerve. The goal is to test the hypothesis that peripheral inflammation or neuropathy will disrupt normal neuronal processing in these pathways. Aim 2 is to study the neural responses of thalamocortical circuit to the behaviorally effective DBS in the rat models of chronic pain. The goal is to test the hypothesis that high frequency stimulation of VPL (ventral posterior lateral nucleus of thalamus) and PAG (periaqueductal gray) restored normal processing in the thalamocortical pathways that are not regulated correctly in the chronic pain condition. Multiple channel single-unit electrophysiological recording techniques in awake freely- moving animals will be employed to reveal the dynamic activity pattern of neurons in thalamocortical areas. Inflammatory pain induced by Freund's complete adjuvant, and spinal nerve ligation induced neuropathic pain models, will be used to mimic two major types of clinical chronic pain syndromes. This study will substantially advance our knowledge about the mechanisms underlying analgesic effect of DBS. Furthermore, success of this study will lay the groundwork for a future goal of using real-time neural network information obtained from recording ensemble thalamocortical neural activity to improve and optimize the effects of DBS in pain patients. Our collaboration will continue a basic investigation of multiple functions of the central brain regions related to pain regulation. PUBLIC HEALTH RELEVANCE: Pain is a common neurological disorder affecting millions of patients. Many of these patients are not responsive to conventional medical treatment. Deep brain stimulation thus provides a promising alternative for alleviate chronic pain. This research project will study the neural mechanisms underlying pain process and the effect of deep brain stimulation on chronic pain in animal models. The study will help us to better apply deep brain stimulation in the clinic to treat intractable pain.